Myocardial infarction in the presence of left ventricular hypertrophy is associated clinically with increased mortality and experimentally with increased infarct size. Reperfusion following coronary occlusion results in decreased infarct size relative to the size of the risk region, and in recovery of segmental function over a 4-week period. It is unknown how left ventricular hypertrophy influences the myocardial response to reperfusion. The aims of this proposal are to examine: 1) the influence of hypertrophy on segmental recovery following coronary occlusion with reperfusion; 2) how left ventricular hypertrophy affects the relationship of segmental function to regional myocardial blood flow, segmental necrosis, infarct size, and the infarct size-risk region ratio after coronary artery occlusion and reperfusion; 3) the inotropic reserve of hypertrophied myocardium after coronary occlusion and reperfusion; and 4) whether combined calcium channel and beta blockade enhances reperfusion-induced recovery of segmental function in the presence of left ventricular hypertrophy. These questions will be addressed using a model of coronary artery occlusion of variable durations followed by reperfusion in dogs with renal hypertension-induced left ventricular hypertrophy. Renal artery stenosis will be induced 6-8 weeks prior to instrumentation. Serial measurements of blood pressure and two-dimensional echocardiographic mass determinations will assess the development of hypertrophy. When LV mass is increased by 25%, the dogs will be instrumented with ultrasonic crystals to measure segmental shortening and endocardial length, and with catheters to measure hemodynamics. Regional myocardial blood flow will be measured with radiolabeled microspheres. Coronary occlusions of 1, 2, and 4 hours will be followed by 4 weeks of reperfusion. Serial measurements of regional systolic wall thickening, endocardial shortening, and hemodynamics will be obtained. At 4 weeks, these parameters will be compared to segmental necrosis, infarct size, infarct to risk region ratio, and regional blood flow in control (non-hypertrophied) and in hypertrophied models. We hypothesize that these experiments will show that left ventricular hypertrophy adversely influences recovery of left ventricular segmental function caused by reperfusion. We hypothesize that hypertrophy will shorten the ischemic duration after which segmental recovery is demonstrable with reperfusion. These findings may help explain the variability of results of clinical trials of thrombolysis during acute myocardial infarction.